INSULIN-INHIBITION OF 5'-ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN-KINASE IN THE HEART RESULTS IN ACTIVATION OF ACETYL-COENZYME-A CARBOXYLASE AND INHIBITION OF FATTY-ACID OXIDATION

Acetyl coenzyme A (CoA) carboxylase (ACC) is an important regulator of fatty acid oxidation in the heart, since it produces malonyl CoA, a p otent inhibitor of mitochondrial fatty acid uptake, Under conditions o f metabolic stress, 5' adenosine monophosphate-activated protein kinas e (AMPK), which is highly expressed in cardiac muscle, can phosphoryla te and decrease ACC activity. In this study, we determined if fatty ac id oxidation in the heart could be regulated by insulin, due to altera tions in AMPK regulation of ACC activity. Isolated working rat hearts were perfused with Krebs-Henseleit solution containing 11 mmol/L gluco se, 0.4 mmol/L [9,10-H-3]palmitate, and either 100 mu U/mL insulin or 1,000 mu U/mL insulin. increasing insulin concentration resulted in a decrease in fatty acid oxidation rates (P < .05), a decrease in AMPK a ctivity (P < .05), and an increase in AGC activity (P < .05) compared with the low insulin group. A negative correlation was observed betwee n AMPK and ACC activity (r = -.76), We conclude that insulin, acting t hrough inhibition of AMPK and stimulation of ACC, is capable of inhibi ting myocardial fatty acid oxidation. Copyright (C) 1997 by W.B. Saund ers Company.